Routine use of next-generation sequencing for preimplantation genetic diagnosis of blastomeres obtained from embryos on day 3 in fresh in vitro fertilization cycles

Fertil Steril. 2015 Apr;103(4):1031-6. doi: 10.1016/j.fertnstert.2014.12.123. Epub 2015 Jan 24.


Objective: To determine the usefulness of semiconductor-based next-generation sequencing (NGS) for cleavage-stage preimplantation genetic diagnosis (PGD) of aneuploidy.

Design: Prospective case-control study.

Setting: A private center for reproductive medicine.

Patient(s): A total of 45 patients underwent day-3 embryo biopsy with PGD and fresh cycle transfer. Additionally, 53 patients, matched according to age, anti-Müllerian hormone levels, antral follicles count, and infertility duration were selected as controls.

Intervention(s): Choice of embryos for transfer was based on the PGD NGS results.

Main outcome measure(s): Clinical pregnancy rate (PR) per embryo transfer (ET) was the primary outcome. Secondary outcomes were implantation and miscarriage rates.

Result(s): The PR per transfer was higher in the NGS group (84.4% vs. 41.5%). The implantation rate (61.5% vs. 34.8%) was higher in the NGS group. The miscarriage rate was similar in the 2 groups (2.8% vs. 4.6%).

Conclusion(s): We demonstrate the technical feasibility of NGS-based PGD involving cleavage-stage biopsy and fresh ETs. Encouraging data were obtained from a prospective trial using this approach, arguing that cleavage-stage NGS may represent a valuable addition to current aneuploidy screening methods. These findings require further validation in a well-designed randomized controlled trial.

Clinical trial registration number: ACTRN12614001035617.

Keywords: Next-generation sequencing; aneuploidy screening; genotyping; preimplantation genetic diagnosis; semiconductor-based sequencer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blastocyst / cytology*
  • Blastocyst / metabolism
  • Blastomeres / cytology
  • Blastomeres / metabolism*
  • Case-Control Studies
  • Diagnostic Tests, Routine / methods
  • Diagnostic Tests, Routine / statistics & numerical data
  • Embryo Transfer / statistics & numerical data
  • Female
  • Fertilization in Vitro* / statistics & numerical data
  • Genetic Testing / methods*
  • Genetic Testing / statistics & numerical data
  • High-Throughput Nucleotide Sequencing* / statistics & numerical data
  • Humans
  • Pregnancy
  • Pregnancy Rate
  • Preimplantation Diagnosis / adverse effects
  • Preimplantation Diagnosis / methods*
  • Preimplantation Diagnosis / statistics & numerical data

Associated data

  • ANZCTR/ACTRN12614001035617